This invention relates to a method for recovering active alkaloids which form a free base soluble in non-polar solvent and a water-soluble acid salt, from plants containing these compounds.
Many plants contain valuable alkaloids, which can be used in treating a variety of conditions. Among the uses for plant-derived alkaloids are the chelidonene group, which have been found to be useful against malignant tumors, papillomatosis of the larnyx, and early forms of lupus erythematosus.
Alkaloids of the chelidonene group have so far been found in the fimbriated poppy (Glaucium fimbrilligerum Boiss.) and in Corydalis ledebourania Kar. et Kir. and Corydalis severtzovii Regal. These alkaloids have also been found in the Papaveraceae, such as the species Bocconia (Macleaya) microcarpa (Maxim) Fedde.
Sanguinaria canadensis, Linn (family Papvaraceae) is commonly known as bloodroot, redroot, puccoon, teterwort, etc., and is a perennial herb native to North America. The plant and its juices have been used for various purposes in pre-historical and historical times. The plant has been used, in particular, as a folk remedy. The plant has generally been used whole, either undried (fresh) or dried. The usual procedure is to powder the dried plant and mix it with a carrier. This folk remedy has been tried for such conditions as asthma, bronchitis, dysentery, ringworm, and a substantial list of other ailments.
The rhizome of the plant has not been used much in modern times. The present principal use of Sanguinaria is as stimulate expectorant in cough syrups and in homeopathic medicine.
As early patent, U.S. Pat. No. 209,331, disclosers the use of bloodroot, zinc chloride, and Kerosene oil in equal proportions for treating open sores. U.S. Pat. No. 433,257, describes a salve of pulverized bloodroot, armenian bole, powdered rosin, lard, and Stockholm tar for use in the treatment of piles. U.S. Pat. No. 2,344,830, discloses the use of a mixture of zinc chloride, stibnite, and bloodroot to fix and outline diseased tissue for excision by surgery.
More recently, it has been discovered that extracts of sanguinaria and other plants of the families Papaveraceae. Fumariaceae, and Berberidaceae such as Macleaya cordata, Bocconia frutescens, Corydalis sevctcozii, C. ledebouni, Argemone mexicanus, and Chelidonium majus contain benzo-c-phenanthridine alkaloids which are believed to have valuable properties in conditioning oral tissue, as well as in preventing and treating gingivitis, periodontitis, and mouth odors.
The pure chemical sanguinarine, chelerythrine, protopine, chelerubine, chelilutine, sanguilatine, macarpine, sanguirubine, allocryptopine, homochelidonene, and berberine, can be isolated form plants other than Sanguinaria. They are also available, although rarely, from some chemical supply houses, semi-purified forms of the alkaloids are commercially available, and these are generally referred to as sanguinarine nitrate and sanguinarine sulfate. These "salts" are the salts of the mixed alkaloids of the plant Sanguinaria: namely, sanguinarine, chelerytherine, and protopine. While few references can be found in the literature regarding the usage of any of the pure benzophenanthridine alkaloids, plants containing such compounds have been used for a wide variety of medical ailments.
Several patents have disclosed the use of extracts of Sanguinaria for such purposes, notably U.S. Pat. No. 4,145,412; U.K. Pat. No. 2,042,336; U.S. Pat. No. 4,376,115; U.S. 4,406,881; German Pat. No. 2,907,406; Belgain Pat. No. 888,843. These patents describe the use Sanguinaria extracts as antimicrobial agents as well as mouth treating agents.
The prior art cited above describes a method of extracting active ingredients from Sanguinaria canadensis by extracting cut or ground bloodroot with methanol for at least 24 hours at an elevated temperature, filtering the liquid extract contained, evaporating the extract to dryness, dissolving the dried residue in chloroform, adjusting the chloroform solution to an acid pH by the addition of hydrocloric acid, filtering the acidified extract, evaporating it to dryness, and dissolving the dried residue in glycerine for mixing with a carrier.
V.A. Chelombit'ko et al., in Khimiko-Farmatsevticheskii Zhurnal, No. 2, 49-52, Feb., 1968, disclose a method of extracting chelerythrine and sanguinarine from plants by soaking the plants in 10% ammonia solution covered with dichloroethane and then in dichloroethane. The solution was alkalified and the alkaloid bases precipitated.
U.S.S.R. Pat. No. 495,311, discloses a method of obtaining greater celandine alkaloids by extracting the leaves of plants containing the alkaloids with aqueous acetone acidified with acetic acid, removing the acetone by distillation, and raising the pH to 10-11 with ammonium hydroxide to precipitate berberine. The precipitate is extracted with trichloromethane to obtain the soluble berberine group alkaloid bases, which can be worked up into berberine, chelidonine hydrochloride, and a mixture of sanguinarine, chelerytherine, and chelilutin.
German Pat. No. 2,856,577 discloses a method of preparing benzophenanthridine alkaloids from plant materials by moistening chopped plant materials with an ammonia solution and subjecting the mixture to a trichloromethane extraction to enrich the alkaloids. Sulfuric acid is added and the solvent is simulataneously distilled off. The residue is basified with ammonia to precipitate the alkaloid free bases which are then filtered off.